Recent developments in the stereoselective synthesis of α-aminoacids

Chiral enolates of imidazolidinones and oxazolidinones from the title amino acids react with carbonyl compounds to afford the corresponding alcohols in excellent yields (see Scheme 5). Furthermore, the addition to aldehydes proceeds with high diastereoselectivity to give, after acid hydrolysis, threo-α-amino-β-hydroxy acids of high enantiomeric purity. Some of the threo-α-amino-β-hydroxy acids prepared in this work are the proteinogenic (S)-threonine (26), the naturally occurring (S)-3-phenylserine (28), and (S)-3-hydroxyleucine (27) as well as the unnatural (S)-4,4,4-trifluorothreonine (30) and (S)-3-(4-pyridyl)serine (31). The N-methylamide of (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoic acid (32), the unique amino acid in the immunosuppressive cyclosporine, was prepared by the new method. This report presents also information suggesting that both steric and stereoelectronic effects are responsible for the good stereoselectivities observed.

Addition of chiral glycine, methionine, and vinylglycine enolate derivatives to aldehydes and ketones in the preparation of enantiomerically pure α-amino-β-hydroxy acids

Resolution and use in α-amino acid synthesis of imidazolidinone glycine derivatives

Fluorine does not belong to the pool of chemical elements that nature uses to build organic matter. However, chemists have exploited the unique properties of fluorine and produced countless fluoro-organic compounds without which our everyday lives would be unimaginable. The incorporation of fluorine into amino acids established a completely new class of amino acids and their properties, and those of the biopolymers constructed from them are extremely interesting. Increasing interest in this class of amino acids caused the demand for robust and stereoselective synthetic protocols that enable straightforward access to these building blocks. Herein, we present a comprehensive account of the literature in this field going back to 1995. We place special emphasis on a particular fluorination strategy. The four main sections describe fluorinated versions of alkyl, cyclic, aromatic amino acids, and also nickel-complexes to access them. We progress by one carbon unit increments. Special cases of amino acids for which there is no natural counterpart are described at the end of each section. Synthetic access to each of the amino acids is summarized in form of a table at the end of this article with the aim to make the information easily accessible to the reader.

Approaches to Obtaining Fluorinated α-Amino Acids.

To exploit the enzymatic method for the synthesis of β-hydroxy-α-amino acids, the genes coding for the Escherichia coli l-threonine aldolase (LTA; EC 2.1.2.1) and Xanthomonus oryzae d-threonine aldolase (DTA) were cloned and overexpressed in E. coli through primer-directed polymerase chain reactions. The purified recombinant enzymes were studied with respect to kinetics, specificity, stability, additive requirement, temperature profile, and pH dependency. DTA requires magnesium ion as a cofactor, while LTA needs no metal ions. These enzymes work well in the presence of DMSO with concentration up to 40%, and DMSO-induced rate acceleration of LTA-catalyzed reaction was observed. Both enzymes use pyridoxal phosphate coenzyme to activate glycine to react with a wide range of aldehydes. LTA gave erythro-β-hydroxy-α-l-amino acids with aliphatic aldehydes and the threo isomer with aromatic aldehydes as kinetically controlled products. On the other hand, DTA formed threo-β-hydroxy-α-d-amino acids as kinetically c...

Enzymatic Synthesis of β-Hydroxy-α-amino Acids Based on Recombinant d- and l-Threonine Aldolases

Synthese en particulier de serine, hydroxy-3 valine, hydroxy-2 phenylserine, phenylserine et methylenedioxy-3,4 phenylserine

General method of diastereo- and enantioselective synthesis of β-hydroxy-α-amino acids by condensation of aldehydes and ketones with glycine

A new class of catalysts of interfacial asymmetrical alkylation is suggested for the synthesis of α-amino acids — positively charged complexes of the transition metals Cu(II), Ni(II), and Pd(II). These complexes consist of several fragments, by variation of which the structure of the catalysts can readily be modified. The complexes are chiral on account of (S)proline derivatives contained in them as one of the fragments. The catalyst complexes (C) were used in the alkylation of amino acid fragments of Ni(II) complexes of the Schiff base of glycine with N-(2-pyridinecarbonyl)-o-aminobenzophenone (Ni-PBP-Gly) and the Schiff base of alanine with N-(2-pyridinecarbonyl)-o-aminobenzaldehyde (Ni-PBA-Ala) under interfacial conditions. After decomposition of the alkylated complexes, phenylalanine and α-methyl-phenylalanine were isolated with yields of 33–87% and optical purity (o.p.) from 3 to 21%, depending on the C used.

Transition metal complexes — A new class of catalysts of interfacial alkylation for the asymmetrical synthesis of α-amino acids

Synthesis of Enantio- and Diastereoisomerically Pure Substituted Prolines via Condensation of Glycine with Olefins Activated by a Carbonyl Group.

1.

The method of liquid chromatography has been used to study the stereoselective effects in complexes of salicylaldehyde and the copper ion with alanine di- and tripeptides.




2.

With a dipeptide copper ion salicylaldehyde reactant ratio equal to 1∶1∶1 the first and second N-terminal amino-acid residues undergo racemization in the dipeptide, the rate of the racemization of the first amino-acid residue in the dipeptide being much greater than the rate for the second. Under these conditions only the first N-terminal residue undergoes racemization in the tripeptide.




3.

When there is an insufficient amount of the copper ion, the ratio between the racemization rates of the two residues in the dipeptide remains unchanged. When there is an insufficient amount of the copper ion, the first and second N-terminal amino-acid residues in the tripeptide under racemization, the racemization rate of the first being much greater than the racemization rate of the second. In the tetrapeptide the racemization rates of the first and second N-terminal amino-acid residues are similar when there is an insufficient amount of the copper ion.




4.

The position of the equilibrium between the diastereomers of the alanine peptides depends on the relative concentrations of the copper ions and the salicylaldehyde in the mixture.

V. A. Tsyryapkin

Papers

General method of diastereo- and enantioselective synthesis of β-hydroxy-α-amino acids by condensation of aldehydes and ketones with glycine

General method of diastereo- and enantioselective synthesis of β-hydroxy-α-amino acids by condensation of aldehydes and ketones with glycine

Transition metal complexes — A new class of catalysts of interfacial alkylation for the asymmetrical synthesis of α-amino acids

Synthesis of Enantio- and Diastereoisomerically Pure Substituted Prolines via Condensation of Glycine with Olefins Activated by a Carbonyl Group.

Determination of stereoselective effects in complexes of salicylaldehyde and a copper ion with alanine di- and tripeptides